POS0248 EXPLORING TUMOUR NECROSIS FACTOR INHIBITOR DRUG LEVELS DURING DISEASE ACTIVITY-GUIDED TAPERING IN PATIENTS WITH INFLAMMATORY ARTHRITIS: SECONDARY ANALYSES FROM THE BIODOPT TRIAL
Authors: M. Sørensen, S. Kristensen, K. B. Lauridsen, K. Duch, L. Dreyer, R. Christensen, E. M. Hauge, A. G. Loft, M. Nyhuus Bendix Rasch, H. C. Horn, P. C. Taylor, K. R. Nielsen, L. Uhrenholt
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Fluctuations in tumour necrosis factor inhibitor (TNFi) drug levels in patients with inflammatory arthritis (IA) during disease activity-guided tapering is not well described. <h3>Objectives</h3> To compare TNFi drug-levels in the tapering group, relative to the control group, from baseline to month 18 based on data from the BIODOPT trial. <h3>Methods</h3> BIODOPT was designed as a pragmatic, multicentre, randomised controlled, open-label trial (EudraCT 2017-001970-41) of 18 months duration [1]. Patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in sustained (≥12 month) low disease activity (LDA) and treated with TNFi at baseline were enrolled and randomised into a disease activity-guided tapering or control in a 2:1 ratio. Blood samples at baseline and month 18 were analysed for TNFi drug levels. Based on previous research, the TNFi drug level category was considered intermediate if values were between: adalimumab 5.0-8.0 mg/L, certolizumab pegol 14.7-40.0 mg/L, etanercept 1.8-4.6 mg/L, golimumab 1.0-3.0 mg/L, or infliximab 1.6-5.0 mg/L. Values greater or lesser were considered as high or low TNFi category, respectively. A mixed Poisson regression with robust variance estimator was used for the analyses on TNFi categories; missing data were imputed as low TNFi category. <h3>Results</h3> Of 129 TNFi-treated patients, 88 were randomised to tapering and 41 to a control arm with standard care. Blood samples at baseline and month 18 were available for: tapering group 89% (78/88) and control group 90% (37/41). As expected, baseline TNFi categories were comparable between groups as presented in <b><i>Figure 1</i></b>. At 18 months, fewer patients in the tapering group were in the high TNFi category, relative risk: RR: 0.53 (95%CI 0.31 to 0.90, <i>P</i>=0.02), <b><i>Table 1</i></b>. Even though more patients in the tapering group were in the low TNFi category at 18 months, the difference was non-significant, RR: 1.47 (95%CI: 0.94 to 2.32, P=0.09). The observed changes in TNFi categories between groups from baseline to 18 months indicates acceptable compliance to the trial interventions. At 18 months, 32% (28/88) in the tapering group and 0% (0/41) in the control group had achieved ≥50% dose reduction of their TNFi and were in LDA. The majority of patients in the tapering group were in the high (39% [11/28]) or intermediate (39% [11/28]) TNFi category at baseline; only 22% (6/28) were in the low TNFi category. Thus, indicating a greater chance of successful tapering for patients with high or intermediate TNFi drug levels at baseline. <h3>Conclusion</h3> Successful TNFi tapering was associated with high or intermediate TNFi levels at baseline. Fewer patients in the tapering group were in the high TNFi category at 18 months; thus, indicating acceptable compliance to the trial interventions. Further research is needed for the implications of therapeutic drug monitoring in the management of rheumatic diseases. <h3>Reference</h3> [1]Uhrenholt L, Christensen R, Dreyer L et al. Disease activity-guided tapering of biologics in patients with inflammatory arthritis: A pragmatic, randomised, open-label, equivalence trial. Scand J Rheumatol 2023 (Accepted for publication) <h3>Acknowledgements</h3> The authors thank patients and research personnel who contributed to the BIODOPT trial. <h3>Disclosure of Interests</h3> Mads Sørensen: None declared, Salome Kristensen: None declared, Karen Buch Lauridsen Speakers bureau: Thermo Fisher Scientific, Kirsten Duch: None declared, Lene Dreyer Speakers bureau: Eli Lilly, Galderma, and Janssen, Grant/research support from: BMS (outside the present work), Robin Christensen: None declared, Ellen-Margrethe Hauge Speakers bureau: AbbVie, Sanofi, Sobi, and SynACT Pharma, Grant/research support from: Aarhus University Hospital from Danish Regions Medicine Grants, Danish Rheumatism Association, Roche, Novartis, and Novo Nordic Foundation, Anne Gitte Loft Speakers bureau: AbbVie, MSD, Novartis and UCB, Consultant of: Eli-Lilly, Janssen-Cilag, MSD, Novartis, and UCB, Mads Nyhuus Bendix Rasch Speakers bureau: Sobi, Hans Christian Horn: None declared, Peter C. Taylor Consultant of: AbbVie, Biogen, Eli-Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Inc, Roche, and Sanofi, Grant/research support from: Galapagos, Kaspar René Nielsen: None declared, Line Uhrenholt Speakers bureau: AbbVie, Eli-Lilly, Janssen, and Novarti.s.